Hyperexcitable primary somatosensory cortex in the MitoPark mouse model of Parkinson's disease

Abstract

The majority of Parkinson's disease patients suffer from decreased tactile acuity or neuropathic pain, both of which contribute to low quality of life and likely exacerbate motor dysfunction. How Parkinson's disease pathology relates to altered somatosensation remains unclear. One potential contributor is the progressive degeneration of dopamine neurons. To assess the extent to which gradual dopamine neuron loss contributes to altered somatosensation, we recorded spontaneous and stimulus-evoked activity in the primary somatosensory cortex of the MitoPark mouse model of Parkinson's disease. MitoPark mice experience progressive dopamine neuron degeneration that is independent of -synuclein. We found that MitoPark layer V regular-spiking (largely pyramidal) neurons, but not fast-spiking (largely parvalbumin-expressing inhibitory) neurons, had elevated spontaneous firing rates relative to littermate controls at late stages of symptom progression. Regular-spiking neurons also became hyperresponsive to tactile stimuli -- more neurons were recruited by stimuli across a wide range of intensities, and these neurons responded with higher firing rates. Fast-spiking neurons, but not regular-spiking neurons, became desynchronized at late stages of symptom progression. These physiological changes coincided with pronounced degeneration of dopamine neurons and axons, which we measured with tyrosine hydroxylase immunostaining in the midbrain, striatum, and primary somatosensory cortex. Altogether, this characterization revealed cell-type-specific changes in the primary somatosensory cortex that are consistent with both decreased tactile acuity and hyperalgesia in Parkinson's disease patients. This suggests that the loss of dopamine neurons, potentially including those that innervate primary somatosensory cortex, contributes to somatosensory impairments associated with Parkinson's disease.